We performed a double-blind study on the effect of oral administration of 10 mg of delta9-tetrahydrocannabinol on specific airway conductance (Gaw/VL) and the maximal expiratory flow at 50% of vital capacity (Vmax 50%) in six control and six asthmatic subjects. In control subjects, there was a slight but statistically significant increase in Gaw/VL after oral administration of delta9-tetrahydrocannabinol; however, there was no significant increase in Vmax 50%. One of the asthmatic patients developed severe bronchoconstriction following administration of delta9-tetrahydrocannabinol; among the remaining five patients, there were variable changes in Gaw/VL and Vmax 50% after oral administration of delta9-tetrahydrocannabinol, but mean changes were not significant. Mild effects on the central nervous system (CNS) were observed in three subjects; six subjects, three of whom had unpleasant mood changes, had more prominent CNS effects. We concluded that oral administration of delta9-tetrahydrocannabinol is unlikely to be of therepeutic value in asthma, since its bronchodilator action was mild and inconstant and was associated with significant CNS effects. Moreover, one asthmatic patient developed severe bronchoconstriction following oral administration of delta 9-tetrahydrocannabinol.

In a single-blind study the short-term effects of oral administration of Th1165a (5, 10, 15, and 20 mg), metaproterenol sulfate (Alupent) (20 mg), and placebo on ventilatory function, pulse rate, and systolic and diastolic blood pressure were compared over a period of six hours in ten patients with stable, reversible obstructive airway disease. Both Th1165a (5, 10, 15 and 20 mg) and metaproterenol administration caused significant bronchodilation of rapid onset (30 minutes), but the bronchodilator effect of Th1165a (10, 15, and 20 mg) was greater and lasted longer (six hours vs three hours) than that of metaproterenol. A dose-dependent bronchodilator effect was recognizable after administration of Th1165a. The 20-mg dose of metaproterenol sulfate and the 5-mg and 10-mg doses of Th1165a produced minimal side effects. Larger doses (15 and 20 mg of Th1165a caused significant increases in pulse rate. Mild and transient tremors were the most common side effect after administration of Th1165a.

In a randomized double-blind 12-week trial of steroid-dependent patients with chronic asthma, ten (59 percent) out of 17 patients receiving beclomethasone dipropionate aerosol in a total daily dose of 400mug were able to discontinue systemic corticosteroid therapy successfully, compared to two (13 percent) out of 15 patients in the placebo group (P=0.002). At the end of the trial, the average 8 am plasma cortisol level in the group receiving beclomethasone was more than twice the pretherapy value, whereas the level in the placebo group showed no significant change. There was no significant difference between the beclomethasone group and the placebo group in the overall incidence of side effects related to the aerosol and the effects of systemic corticosteroid withdrawal. Oral candidiasis was not found in any patient receiving beclomethasone dipropionate aerosol. Allergic nasal symptoms were disabling in many patients when the oral dosage of corticosteroids was tapered.

In order to objectively document the accepted clinical efficacy of ampicillin in treating bacterial exacerbations of chronic bronchitis, as well as to evaluate the efficacy of methacycline, a double-blind crossover study was designed. Twenty patients with chronic bronchial disease were treated for two separate acute bacterial exacerbations, once with 2 gm of ampicillin daily, and once with 600 mg of methacycline daily, for 14 days. There were a few significant differences when comparing the efficacy of the antimicrobials. For example, the daily volume of sputum significantly went from 35.6 ml initially to 20.5 ml at the end of treatment with methacycline, and from 37.4 to 18.0 ml with ampicillin. Sputum neutrophils excreted per day went from 446 to 147 million with methacycline and from 433 to 94 million with ampicillin. Gram-positive diplococci and cocci on gram stains of sputum significantly decreased form 10.6 to 3.3 with methacycline and from 16.8 to 2.1 with ampicillin. This investigation objectively documents with accepted clinical efficacy of ampicillin and proves methacycline to be an equally effective agent.

Twenty-five steroid-dependent severely asthmatic patients, ranging in age from 20 to 67 years, were hospitalized. Baseline laboratory and pulmonary function testing was followed by reduction of prednisone therapy to 5 mg daily and by entry into a randomized double-blind study of placebo vs active aerosol triamcinolone acetonide (300mug four times daily). In this four-week trial, aerosol triamcinolone acetonide further reversed airway obstruction and proved to be an effective substitute for large oral doses of steroids in steroid-dependent patients with severe asthma. No significant improvement occurred in the maximum midexpiratory flow or the maximum velocity of air flow after 50 percent or 75 percent of the vital capacity had been expelled. There was no significant difference in the frequency of untoward effects between the groups taking aerosol triamcinolone acetonide and its vehicle. No patient demonstrated any definite return of adrenal function.

Twenty-seven patients underwent studies of unilateral lung function by the lateral-position test (LPT) and by computer-analyzed radionuclide imaging of ventilation and perfusion. The patients were divided into two groups, symmetric or asymmetric, on the basis of the physical examination of the chest and the chest radiograph. In patients with symmetry, the estimate of unilateral lung function by the LPT and isotopic estimates for unilateral lung volume, unilateral distribution of tidal volume, and unilateral perfusion, agreed within 2 percent, 4 percent, and 3 percent, respectively. In patients with asymmetry, the differences were 9 percent, 8 percent, and 13 percent. In settings of marked unilateral ventilation-perfusion imbalance, the LPT primarily reflected ventilation. Prediction of unilateral ventilatory function based upon the LPT and spirometric measurements agreed closely with unilateral ventilation determined isotopically by 133xenon, even in the presence of chronic obstructive lung disease. Our results confirm that the LPT provides valid information about unilateral lung function.

Sixteen men with well-documented angina pectoris and without previous myocardial infarction performed a multistage exercise stress test to determine their levels of exercise-induced limitations, characterized by onset of chest discomfort or electrocardiographic ischemic changes, or both. Following a control study, each subject was assigned randomly to either a placebo- or vasodilator-treated group, received chewable medication, and was retested 30 minutes after chewing the medication. Blood pressure, heart rate, and electrocardiographic changes were measured during rest, peak exercise, and recovery. A phonocardiogram, carotid-pulse contour, and single-lead electrocardiogram were recorded simultaneously at supine rest before and immediately after exercise, and systolic time intervals were measured. Results indicated that chewable isosorbide dinitrate reduced systolic blood pressure and the triple product (systolic blood pressure X heart rate X ejection time) significantly during rest and reduced the left ventricular ejection time corrected for heart rate both at rest and peak exercise; no significant differences were observed in the placebo group. The ability to achieve an increased workload was observed in both groups, and the threshold for ischemic manifestations occurred at comparable triple-product levels in both during pretreatment and posttreatment studies.

The hemodynamic response to nitroglycerin administration, to sublingual or oral administration of isosorbide dinitrate, or to a placebo was evaluated and compared in 37 patients with unstable angina pectoris under resting, pain-free conditions. Patients with congestive heart failure were not included in this study. Serial measurements of mean arterial blood pressure (MAP), pulmonary arterial end-diastolic pressure (PAEDP), cardiac index (CI), and heart rate (HR) were obtained for one hour following nitroglycerin administration and for four hours following sublingual or oral administration of isosorbide dinitrate. Echocardiographic end-diastolic volume (EDV) measurements were obtained for the groups receiving isosorbide dinitrate or placebo. There was a significant (P less than 0.05 or less than 0.1) reduction of the MAP (5 to 10 mm Hg) that persisted for more than four hours following both sublingual and oral administration of isosorbide dinitrate. The changes in the PAEDP, HR, and CI following sublingual or oral administration of isosorbide dinitrate were small and not significant. In the group receiving isosorbide dinitrate sublingually, the EDV was reduced by more than 30 ml below the placebo group (P less than 0.1) for up to four hours. The effects of nitroglycerin administration were similar in magnitude but of much shorter duration (three to four hours for sublingual and oral administration of isosorbide dinitrate vs 15 to 30 minutes for nitroglycerin). These data demonstrate that the duration of the hemodynamic effects of sublingually and orally administered isosorbide dinitrate in patients with unstable angina pectoris and normal resting hemodynamics is 8 to 12 times longer than that of nitroglycerin.

A double-blind study of the effects of phlebotomy was carried out in 18 patients with polycythemia secondary to severe hypoxemic lung disease. Eleven subjects underwent a single phlebotomy of 10 percent of their blood volume, and eight patients serving as controls underwent a sham procedure. Eight of the phlebotomized subjects, but none of the controls, reported subjective clinical improvement (P less than 0.005). Subjects who noted improvement after venesection had higher hematocrit readings than those who did not (P less than 0.02). Symptomatic relief seemed to be most dramatic in those with clinical evidence of congestive heart failure. In contrast to this clear-cut subjective improvement, phlebotomy did not alter objective indices of airway obstruction, lung elastic recoil, pulmonary gas exchange, or exercise tolerance in either the phlebotomized or the control group. Thus, although phlebotomy produced subjective benefit in the majority of patients studied, it was not associated with objective improvement in lung function or exercise tolerance.

Endotracheal administration of gentamicin has been compared to the endotracheal administration of aminosidin plus polymyxin B as a preventive measure against tracheobronchial infections in 25 and 22 tracheotomized patients respectively who had been admitted to a neurosurgical unit. Both series were comparable as far as underlying disease, duration of hospitalization, surgical therapy. Both regimens were similarly effective from the bacteriologic and clinical points of view. Both regimens were similarly effective in preventing colonization of bronchial secretions by potential pathogens and were associated with a similar frequency of infectious episodes (eight in each group). The use of aminosidin-polymyxin B combination was associated with a lower incidence of emergence of gentamicin resistant strains, but the endotracheal administration of gentamicin was better tolerated than that of the combination. It is concluded that the combination of aminosidin-polymyxin is a useful alternative to gentamicin for the prevention of bronchopulmonary infections in unconscious tracheotomized patients.

Acute effects of oral terbutaline (5 mg), ephedrine (25 mg) and placebo on bronchial dynamics, heart rate, systolic and diastolic pressure and arterial blood gases at rest were compared over a period of 7 hours in 20 subjects with bronchial asthma using a double-blind crossover technique. Both terbutaline and ephedrine caused significant bronchodilation, but the effect of terbutaline on specific airway conductance (SGA) was significantly greater (peak mean increase in SGA 0.069 vs 0.027 L/sec/cm H2O/L), had an earlier onset (30 minutes vs 1 hour) and lasted longer (7 hours vs 4 hours) than that of ephedrine. Slight but significant increases in arterial Po2 were noted following institution of both ephedrine and terbutaline, suggesting improvement in ventilation-perfusion relationships. Both drugs caused modest but statistically significant increases in heart rate of 8.4-10.9 beats/min and the mean peak increase following terbutaline (8.4 beats/min) was comparable to that following ephedrine. In constrast to ephedrine, terbutaline caused significant, although slight, increases in systolic pressure and decreases in diastolic pressure, indicating that this drug, in the dose recommended for clinical use, is not free of cardiovascular effects.

The effect of the regular use of neublized isoproterenol in 14 patients with symptomatic chronic obstructive lung disease (COLD) was evaluated in a double-blind crossover 16-week study. FEV1, FVC and SGaw were measured before and 45 minutes after bronchodilator therapy every two weeks, while arterial blood gases were measured every eight weeks, before and 45 minutes after bronchodilator therapy. When the patients were considered as a group, there was no significant difference in mean symptom scores or objective pulmonary functions during the drug and placebo periods. Four patients had significantly higher (p less than .05) and two patients significantly lower mean values for at least one of the pulmonary function tests during the isoproterenol period. The patient who is most likely to benefit from isoproterenol on a regular basis appears to have the following characteristics; (1) consistent improvement in pulmonary function tests 45 minutes after use of nebulized bronchodilator; (2) moderate rather than severe COLD; and (3) a relatively normal DLCO.

The antiarrhythmic activity of diphenidol, an antiemetic, has been demonstrated both in electrophysiologic studies of patiens and in experimental arrhythmias in animals. Accordingly, 18 patients with tachyarrhythmias were treated with intravenous diphenidol in doses of 0.5 to 1.5 mg/kg. In six patients with atrial arrhythmias, there was no notable effect. Similarly, 12 patients with premature ventricular contractions were treated and studied. In six of them, ectopic beats were abolished, at least transiently; in three the number of ventricular premature contractions decreased; in two there was no effect; and in one, the number of premature beats was increased. Of the total number of 18 patients, 14 suffered adverse effects related to the central nervous system. These adverse effects were of such severity as to suggest that further studies with diphenidol as an antiarrhythmic are not warranted.

A case is reported in which a previously healthy individual, having received an inadequate course of chicken soup in treatment of mild pneumococcal pneumonia, experienced a severe relapse, refractory to all medical treatment and eventually requiring thoracotomy. The pharmacology of chicken soup is reviewed and the dangers of abrupt termination of therapy are stressed.